Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti-B7H3 immunotherapy

AbstractOmburtamab is a B7H3-specific murine monoclonal antibody. B7H3 (CD 276) is a member of the B7 family of immune checkpoint co-inhibitory receptors overexpressed on many human malignancies. Radioimmunotherapy with 124I- or 131I-omburtamab administered in the cerebrospinal fluid (CSF), intraperitoneal or intratumoral cavity is currently under investigation for the treatment of CNS malignancies. The immunologic effects of anti-B7H3 therapy are not fully elucidated. A 6-year-old male was diagnosed with metastates of neuroblastoma to the received intraventricular 131I-omburtamab on an IRB-approved protocol. A treatment cycle consisted of a 2 mCi dosimetry dose and a 50 mCi treatment dose. Dosimetry by serial imaging, pharmacokinetics and safety were investigated. Clinical status, magnetic resonance imaging, CSF cell count and cytology were evaluated pre- and post-131I-omburtamab at 5 and 26 weeks. The patient did well with cycle 1. Three hours after the dosimetry dose of cycle 2, he developed a fever (39 °C), chills and headache. Blood and CSF samples were sent for culture. CSF was notable for nucleated cell pleocytosis with profound mast cell proliferation consistent with chemical meningitis. He was treated with supportive care; symptoms resolved over 48 h. Further therapy with 131I-omburtamab was electively discontinued. CSF cell count 5 weeks later demonstrated resolution of CSF pleocytosis. Local–regional administration of intraventricular 131I-omburtamab targeting B7H3 can result in a profound nucleated CSF pleocytosis with mastocytosis consistent with an acute allergic reaction.

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Correction to: Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti‑B7H3 immunotherapy

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02942-3 ◽

2021 ◽

Author(s):

Kim Kramer ◽

Maria A. Donzelli ◽

Melissa S. Pessin

Keyword(s):

Cell Proliferation ◽

Cerebrospinal Fluid ◽

Mast Cell ◽

Intraventricular Administration

A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02942-3

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Analysis of the risk of shunt failure or infection related to cerebrospinal fluid cell count, protein level, and glucose levels in low-birth-weight premature infants with posthemorrhagic hydrocephalus

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2011.05.015 ◽

2011 ◽

Vol 2011 ◽

pp. 270-271

Author(s):

P. Klimo

Keyword(s):

Cerebrospinal Fluid ◽

Birth Weight ◽

Low Birth Weight ◽

Cell Count ◽

Premature Infants ◽

Protein Level ◽

Shunt Failure ◽

Posthemorrhagic Hydrocephalus ◽

Glucose Levels ◽

Fluid Cell

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Faculty Opinions recommendation of KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9549956.10205054 ◽

2011 ◽

Author(s):

Richard L Stevens

Keyword(s):

Cell Proliferation ◽

Mast Cell ◽

Mitf Expression

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Lung mast cell density and distribution in chronically hypoxic animals

Journal of Applied Physiology ◽

10.1152/jappl.1977.42.2.174 ◽

1977 ◽

Vol 42 (2) ◽

pp. 174-178 ◽

Cited By ~ 28

Author(s):

A. Tucker ◽

I. F. McMurtry ◽

A. F. Alexander ◽

J. T. Reeves ◽

R. F. Grover

Keyword(s):

Cell Proliferation ◽

Pulmonary Hypertension ◽

Mast Cell ◽

Mast Cells ◽

Cell Density ◽

Mammalian Species ◽

Cell Hyperplasia ◽

Mast Cell Density ◽

Lung Mast Cell ◽

Mast Cell Hyperplasia

Changes in the density and distribution of pulmonary mast cells were determined in six mammalian species exposed to hypobaric hypoxia (PB = 435 Torr) for 19–48 days. Control animals were studied at 1,600 m (PB = 635 Torr). Total lung mast cell hyperplasia was observed only in calves exposed to high altitude. Pigs, rats, and sheep exhibited small, but insignificant, increases in mast cell density. Perivascular mast cell proliferation adjacent to vessels of 30–500 mum in diameter was seen in both calves and pigs. Bronchial, alveolar septal, and systemic tissue (tongue) mast cell hyperplasia was not observed in any of the species. Three indices of pulmonary hypertension (right ventricular hypertrophy, medial thickness of pulmonary arteries, and pulmonary arterial pressure) correlated with perivascular mast cell density. The findings indicate that perivascular mast cell proliferation may relate more to the morphological pulmonary vascular changes and to pulmonary hypertension than to hypoxia, leading to the speculation that mast cells increase in number in response to the hypertension, rather than to mediate and maintain the hypertension.

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Cerebrospinal fluid cytomorphologic findings in 41 intracranial tumors: a retrospective review

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1995000200006 ◽

1995 ◽

Vol 53 (2) ◽

pp. 218-226 ◽

Cited By ~ 6

Author(s):

Maria José Sá ◽

Rui Vaz ◽

Celso Cruz

Keyword(s):

Cerebrospinal Fluid ◽

Cell Count ◽

Tumor Cells ◽

Retrospective Review ◽

Ct Scanning ◽

Meningeal Carcinomatosis ◽

Cerebral Metastasis ◽

Unexpected Finding ◽

Intracranial Tumors ◽

Neoplastic Cells

The main objective of this retrospective review of clinical and cerebrospinal fluid (CSF) data from 41 patients with intracranial tumors diagnosed between 1975 and 1989, is to report the role that the finding of neoplastic cells in CSF plays, specially when cerebral CT-scanning and MRI were not currently done. Another objective is to study the CSF proteic abnormalities in cerebral tumors. CSF cell count, cytomorphologic pictures obtained after sedimentation and protein findings are described. Tumor cells were seen in 12 cases (29%): medulloblastomas - 6, meningeal carcinomatosis - 3, multiforme glioblastoma - 1, ependymoma -1, cerebral metastasis -1; in two cases it was an unexpected finding. We noticed that tumoral localization next to the ventricles favoured cell exfoliation. Although pleocytosis was rare and uncorrelated with the presence of neoplastic cells, pathological cytomorphologic pictures appeared in most of the cases including all "positive" ones. Our results stress that the appearance of neoplastic cells in CSF remains helpful specially when it is an unexpected finding.

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Mucosal mast cell proliferation following normal and heterotopic infections of the nematodeNippostrongylus brasiliensisin rats

Apmis ◽

10.1111/j.1699-0463.1994.tb05208.x ◽

1994 ◽

Vol 102 (7-12) ◽

pp. 589-596 ◽

Cited By ~ 8

Author(s):

NAOKI ARIZONO ◽

MINORU YAMADA ◽

TATSUYA TEGOSHI ◽

MANABU OKADA ◽

RYUICHI UCHIKAWA ◽

...

Keyword(s):

Cell Proliferation ◽

Mast Cell ◽

Mucosal Mast Cell

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Marked elevation of cerebrospinal fluid white blood cell count: An unusual case of Streptococcus pneumoniae meningitis, differential diagnosis, and a brief review of current epidemiology and treatment recommendations

Journal of Emergency Medicine ◽

10.1016/j.jemermed.2004.12.017 ◽

2005 ◽

Vol 29 (1) ◽

pp. 37-41 ◽

Cited By ~ 7

Author(s):

Jay Menaker ◽

Ian Bebvon K. Martin ◽

Jon Mark Hirshon

Keyword(s):

Cerebrospinal Fluid ◽

Differential Diagnosis ◽

Streptococcus Pneumoniae ◽

Blood Cell ◽

Cell Count ◽

White Blood Cell Count ◽

White Blood Cell ◽

Unusual Case ◽

Blood Cell Count ◽

Marked Elevation

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High fat diet and mast cell count in rat mesenterium

Cellular and Molecular Life Sciences ◽

10.1007/bf02158655 ◽

1958 ◽

Vol 14 (5) ◽

pp. 184-184 ◽

Cited By ~ 9

Author(s):

J. Fodor ◽

P. Fábry ◽

Z. Lojda

Keyword(s):

Mast Cell ◽

Cell Count ◽

High Fat Diet ◽

High Fat ◽

Mast Cell Count

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Inflammatory cerebrospinal fluid analysis in cats: Clinical diagnosis and outcome

Journal of Feline Medicine and Surgery ◽

10.1016/j.jfms.2004.07.001 ◽

2005 ◽

Vol 7 (2) ◽

pp. 77-93 ◽

Cited By ~ 27

Author(s):

M. Singh ◽

D.J. Foster ◽

G. Child ◽

W.A. Lamb

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Cell Count ◽

Clinical Signs ◽

Central Nervous System Disease ◽

Nervous System Disease ◽

Differential Count ◽

System Disease ◽

Csf Analysis

The medical records of 62 cats with clinical signs of central nervous system disease and accompanying inflammatory cerebrospinal fluid (CSF) analysis were examined retrospectively to determine if signalment, clinical signs, CSF analysis and ancillary testing could accurately predict the type of central nervous system disease that was present. An inflammatory CSF was defined as one in which a total nucleated cell count was greater than 5 cells/μl or one in which the total nucleated cell count was normal but the nucleated cell differential count was abnormal. Sex, degree of CSF inflammation, neuroanatomical location and systemic signs provided little contributory information to the final diagnosis. In 63% of the cases a presumptive diagnosis could be made based on a combination of clinical signs, clinicopathological data and ancillary diagnostic tests. CSF analysis alone was useful only in the diagnosis of cats with feline infectious peritonitis, Cryptococcus species infection, lymphoma and trauma. Overall, despite extensive diagnostic evaluation, a specific diagnosis could not be made in 37% of cats. The prognosis for cats with inflammatory CSF was poor with 77% of cats surviving less than 1 year.

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